One long range objective of this research program is the synthesis of biologically and structurally interet=sting alkaloids. A second objective is the development and evaluation of methodology for the synthesis of nitrogen-containing organic compounds. One specific goal of this project is the synthesis of the oxindole alkaloids gelsemine and 21-oxogelsemine. This will be accomplished using methodology that revolves around free radical cyclizations and amine- oxetane reactions of general interest to the area of alkaloid synthesis. A subgoal of this project is the proparation of gelsemine substructures to be submitted for evaluation in biological screens related to cancer, viral, cardiovascular, gastrointestinal and CNS disorders. A second goal of this project is the synthesis of clavepictine A and clavepictine B, quinolizidine alkaloids reported to have antitumor properties. The synthetic approach will be enantioselective and should establish the absolute configuration of these marine natural products. A subgoal of this project will be the preparation and biological evaluation of selected clavepictine analogs in an attempt to identify the pharmacophore of these compounds. This research will examine synthetic and stereochemical aspects of immonium ion chemistry of general interest to alkaloid synthesis. The manzamines are a small family of beta-carboline alkaloids recrntly isolated from marine sources and reported to have potent antitumor activity. The final objective of the proposed research is a synthesis of manzamine A, the most active member of this family of compounds. A new route to pyrrolo[2,3-i]isoquinolines will serve as the starting point for this research. It is hoped that contributions to the areas of medium and large ring lactam and amine synthesis will be derived from this project. A subgoal of this project will be the evaluation of new nitrogen-containing structures in the biological screens cited above.